Pitavastatin or a salt thereof has activity which specifically and antagonistically inhibits an HMG-CoA reductase which is a rate-controlling enzyme of the biosynthetic pathway of cholesterol and is clinically used in the treatment of hypercholesterolemia, familial hypercholesterolemia and the like on the basis of exhibiting a cholesterol-lowering effect, a triglyceride-lowering effect, inhibitory effect on an arteriosclerosis progression and the like.
However, HMG-CoA reductase inhibitors such as pitavastatin, pravastatin, fluvastatin and atorvastatin have a 7-substituted-3,5-dihydroxy-6-heptenoic acid (or a 7-substituted-3,5-dihydroxy heptanoic acid) structure, and have problems in that a lactone is produced and stability is poor in a low pH environment. In a case where stability of a drug is poor, there is a possibility that efficacy of the drug is decreased and safety is impaired. Accordingly, it is necessary to stabilize pitavastatin or a salt thereof which is an active ingredient, in a pitavastatin-containing preparation.
As a stabilization method of an HMG-CoA reductase inhibitor-containing preparation, a method of blending a basification agent which gives a pH of 9 or more with an aqueous dispersion of a pravastatin-containing preparation (refer to Patent Literature 1), a method of blending an alkaline medium which can give a pH of at least 8 with an aqueous solution or a dispersion of a fluvastatin-containing preparation (refer to Patent Literature 2), a method of blending a stabilizing metal salt additive with an atorvastatin-containing preparation (refer to Patent Literature 3) and a method of adding a basic substance such that an aqueous solution or a dispersion of a pitavastatin-containing formulation has a pH of 7 or more to 8 or less (refer to Patent Literature 4) are known.
However, in Patent Literatures 1 to 3, there is no specific description for the stabilization of the pitavastatin-containing preparation. Moreover, in Patent Literature 4, the stabilization of the pitavastatin-containing preparation seems to be achieved, but there are also problems in that the stabilization is insufficient, and when a pH is more than 8, the color tone of the outward appearance changes.
As described above, in methods known in the related art, it has not been possible to obtain a preparation with sufficient stability and without the change of the color tone of the outward appearance in the pitavastatin-containing preparation.